scholarly journals Evaluation of renal biomarkers, including symmetric dimethylarginine, following gentamicin-induced proximal tubular injury in the rat

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0006542020
Author(s):  
Diane M Hamlin ◽  
A. Eric Schultze ◽  
Michael J. Coyne ◽  
Donald J. McCrann ◽  
Rebekah Mack ◽  
...  
Keyword(s):  
Renal Function ◽  
Control Group ◽  
Analytical Sensitivity ◽  
Symmetric Dimethylarginine ◽  
Serum Cystatin C ◽  
Rat Serum ◽  
Proximal Tubular ◽  
Renal Biomarker ◽  
Biomarker Evaluation ◽  
Dose Levels

Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney were performed. Prior to biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50 mg/kg and the 100 mg/kg dosage levels in the 4 and 10-dose treatment groups compared to controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with µALB being most responsive and OPN least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA as compared to other excretory renal function markers in a rat gentamicin acute toxicity model. In this study serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.

scholarly journals 1962. Renal Outcomes for Participants Taking F/TAF vs. F/TDF for HIV PrEP in the DISCOVER Trial

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S64-S64
Author(s):  
Anthony Mills ◽  
Kimberly Workowski ◽  
Thomas Campbell ◽  
Paul Benson ◽  
Gordon Crofoot ◽  
...  
Keyword(s):  
Renal Function ◽  
Study Drug ◽  
Tubular Function ◽  
Full Cohort ◽  
Renal Outcomes ◽  
Proximal Tubular ◽  
Renal Biomarker ◽  
Proximal Tubular Function ◽  
Tenofovir Alafenamide ◽  
Sex With Men

Abstract Background In the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here, we report on the renal outcomes of F/TAF and F/TDF among all DISCOVER participants and in those on baseline F/TDF PrEP who were randomized to F/TAF. Methods In total, 5387 men who have sex with men (MSM) and transgender women (TGW) at risk for HIV were randomized 1:1 to receive blinded F/TDF or F/TAF taken once daily (full cohort). Of these, 905 were on F/TDF PrEP at enrollment; of whom, 465 were randomized to F/TAF. Renal function and safety assessments included urinalysis (UA), estimated glomerular filtration rate (eGFRCG), urine protein:creatinine (Cr) ratio (UPCR), markers of proximal tubular function (β2-microglobulin:Cr ratio [β2M:Cr] and retinol-binding protein:Cr ratio [RBP:Cr]) and investigator-reported renal adverse events (AEs). Week 48 data are presented. Results In the full cohort, F/TAF was associated with more favorable changes in eGFRCG, β2M:Cr, and RBP:Cr compared with F/TDF (Table 1). Treatment-emergent proteinuria by UA was more common with F/TDF than F/TAF (24.3% vs. 21.3% P = 0.009), as were treatment-emergent elevations in UPCR >200 mg/g (35 [1.5%] vs. 16 [0.7%], P = 0.005). Compared with F/TDF, participants taking F/TAF had numerically fewer study drug-related renal AEs, severe study drug-related renal AEs, and discontinuations due to renal AEs (Table 2). Proximal renal tubulopathy (Fanconi syndrome) was reported in one participant in the F/TDF arm and none in the F/TAF arm. In participants on F/TDF PrEP at enrollment who were randomized to F/TAF, statistically significant increases in eGFRCG were apparent as early as week 4 (Table 1 and Figure 1), as were decreases in tubular proteinuria (Table 1). Renal biomarker changes in PrEP-naïve participants mirrored those in the full cohort. Conclusion Through 48 weeks, MSM and TGW taking F/TAF for PrEP had significantly better measures of renal function and fewer study-drug-related renal AEs compared with those taking F/TDF; switching from F/TDF to F/TAF was associated with improvements in eGFRCG and tubular function biomarkers. F/TAF for PrEP is effective and has a superior renal safety profile compared with F/TDF. Disclosures All Authors: No reported Disclosures.

scholarly journals Comparative assessment of renal function by cystatin C level in patients with hypertension and extrasystole

2020 ◽  
pp. 11-17
Author(s):  
A. V. Ivankova ◽  
N. V. Kuzminova ◽  
S. E. Lozinsky ◽  
V. P. Ivanov
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Creatinine Level ◽  
Cystatin C ◽  
Blood Pressure Monitoring ◽  
Blood Pressure Measurement ◽  
Left Ventricular ◽  
Control Group ◽  
Ventricular Extrasystole ◽  
Serum Cystatin C

Although the tight connection of the cardiovascular system and the kidneys is well known, using of cystatin C (Cys-C) opens new horizons in studying early renal failure stages. The study aimed to compare the functional status of the kidneys in patients with hypertension and extrasystole to the level of Cys-C. 156 patients with stage II hypertension (EH II) were examined. 124 of them had frequent symptomatic extrasystoles (74 – of supraventricular origin and 50 – ventricular), 32 patients had no arrhythmias, and were referred to the comparison group. The control group consisted of 30 healthy people with normal blood pressure (BP). All patients underwent a complete clinical examination, blood pressure measurement, daily blood pressure monitoring, daily electrocardiogram monitoring, echocardiography, and determination of renal function (creatinine, blood electrolytes, serum cystatin C) followed by calculation of glomerular filtration rate (GFR). The level of Cys-C in patients with hypertension was significantly higher (p<0.001) compared with healthy individuals. Among patients with arrhythmias, the highest level of Cys-C was noted in patients with ventricular arrhythmias. The correlation analysis showed that the level of Cys-C was higher in the presence of frequent extrasystoles (namely of ventricular origin), smoking, high blood pressure, increased systolic and pulse blood pressure, the presence of concentric left ventricular hypertrophy, dyslipidemia, increased creatinine level and decreased GFR. All three EH II patient groups had significantly lower GFR (calculated by creatinine level) (p<0.001). The lowest creatinine-based GFR was revealed in patients with ventricular extrasystole. All patients with EH II had significantly lower Cys-C based GFR than the control group (p<0.001). Mean Cys-C-based GFR values in patients with extrasystole were significantly lower than in patients without extrasystole (p<0.03). The analysis of GFR levels depending on the extrasystole origin was provided. The lowest level of GFR was recorded in patients with ventricular extrasystole. It was significantly different from the patients with supraventricular extrasystole (p=0.02). Our findings confirm the opinion of other researchers that Cys-C is an early marker of renal dysfunction in patients with hypertension, which is more sensitive than creatinine. Another finding is that ventricular extrasystole is more hemodynamically and metabolically unfavorable compared to supraventricular based on clinical and prognostic evaluation.

scholarly journals Assessment of Subclinical Renal Glomerular and Tubular Dysfunction in Children with Beta Thalassemia Major

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 100
Author(s):  
Asmaa A. Mahmoud ◽  
Doaa M. Elian ◽  
Nahla MS. Abd El Hady ◽  
Heba M. Abdallah ◽  
Shimaa Abdelsattar ◽  
...  
Keyword(s):  
Cystatin C ◽  
Kidney Injury ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Good Survival ◽  
Control Group ◽  
Healthy Children ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
Beta Thalassemia Major

Background: A good survival rate among patients with beta thalassemia major (beta-TM) has led to the appearance of an unrecognized renal disease. Therefore, we aimed to assess the role of serum cystatin-C as a promising marker for the detection of renal glomerular dysfunction and N-acetyl beta-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as potential markers for the detection of renal tubular injury in beta-TM children. Methods: This case-control study was implemented on 100 beta-TM children receiving regular blood transfusions and undergoing iron chelation therapy and 100 healthy children as a control group. Detailed histories of complete physical and clinical examinations were recorded. All subjected children underwent blood and urinary investigations. Results: There was a significant increase in serum cystatin-C (p < 0.001) and a significant decrease in eGFR in patients with beta-TM compared with controls (p = 0.01). There was a significant increase in urinary NAG, KIM-1, UNAG/Cr, and UKIM-1/Cr (p < 0.001) among thalassemic children, with a significant positive correlation between serum cystatin-C, NAG and KIM-1 as regards serum ferritin, creatinine, and urea among thalassemic patients. A negative correlation between serum cystatin-C and urinary markers with eGFR was noted. Conclusion: Serum cystatin-C is a good marker for detection of glomerular dysfunction. NAG and KIM-1 may have a predictive role in the detection of kidney injury in beta-TM children.

scholarly journals Assessment of symmetric dimethylarginine as a biomarker of renal function in hyperthyroid cats treated with radioiodine

2019 ◽  
Vol 33 (2) ◽  
pp. 516-522 ◽  
Author(s):  
Eva Buresova ◽  
Emmelie Stock ◽  
Dominique Paepe ◽  
Lisa Stammeleer ◽  
Eva Vandermeulen ◽  
...  
Keyword(s):  
Renal Function ◽  
Symmetric Dimethylarginine

scholarly journals Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents

2016 ◽  
Vol 11 ◽  
pp. BMI.S39199 ◽  
Author(s):  
Habib Mawad ◽  
Louis-Philippe Laurin ◽  
Jean-François Naud ◽  
François A. Leblond ◽  
Nathalie Henley ◽  
...  
Keyword(s):  
Renal Function ◽  
Contrast Agents ◽  
Cystatin C ◽  
Normal Renal Function ◽  
Serum Levels ◽  
Serum Cystatin C ◽  
Baseline Serum ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Novel Biomarkers ◽  
Neutrophil Gelatinase

Objective The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. Methods We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. Results Baseline serum creatinine was 57.8 ± 34.5 μmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels. Conclusions Urinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function.

Nephrotoxicity and its prevention by catechin in ferric nitrilotriacetate promoted oxidative stress in rats

2004 ◽  
Vol 23 (3) ◽  
pp. 137-143 ◽  
Author(s):  
Kanwaljit Chopra ◽  
Devinder Singh ◽  
Vikas Chander
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Thiobarbituric Acid ◽  
Control Group ◽  
Morphological Alterations ◽  
Group Iii ◽  
Ferric Nitrilotriacetate ◽  
Group I ◽  
Rats And Mice

Intraperitoneal injection of ferric nitrilotriacetate (Fe-NTA) to rats and mice results in iron-induced free radical injury and cancer in kidneys. This study was designed to investigate the effect of catechin, a bioflavonoid with antioxidant potential, on Fe-NTA-induced nephrotoxicity in rats. Four groups were employed in the present study. Group I served as control group, Group II animals received Fe-NTA (8 mg iron/kg body weight i.p.), Group III animals were given 40 mg/kg catechin p.o. twice a day for 4 days and on the 5th day Fe-NTA was challenged, and Group IV animals received catechin alone for 4 days. Renal function was assessed by measuring plasma creatinine and blood urea nitrogen. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase, glutathione reductase and superoxide dismutase. One hour after a single intraperitoneal (i.p.) injection of Fe-NTA (8 mg iron/kg), a marked deterioration of renal architecture, renal function and severe oxidative stress was observed. Pretreatment of animals with catechin markedly attenuated renal dysfunction, reduced elevated thiobarbituric acid reacting substances (TBARS), restored the depleted renal antioxidant enzymes and normalized the renal morphological alterations. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction, and suggest a protective effect of catechin on Fe-NTA-induced nephrotoxicity in rats.

scholarly journals Prediction of renal dysfunction in patients with obstructive icterus

2011 ◽  
Vol 64 (9-10) ◽  
pp. 503-506 ◽  
Author(s):  
Suzana Raicevic-Sibinovic ◽  
Aleksandar Nagorni ◽  
Vesna Brzacki ◽  
Mirjana Radisavljevic
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Concentration Index ◽  
Surgical Intervention ◽  
Urine Osmolality ◽  
Sodium Concentration ◽  
Control Group ◽  
Osmotic Concentration ◽  
Creatinine Concentration ◽  
Urinary Osmolality

Introduction. Renal dysfunction is one of complications in patients with obstructive icterus. It is important to recognize it early and take adequate measure to prevent its occurrence. One third of the patients with obstructive icterus have deterioration of renal function before surgical intervention. The aim of the research was to assess the renal dysfunction markers in patients with obstructive icterus. The following factors were examined: diuresis, urinary sodium concentration, sodium excretory fraction, urine osmolality, osmotic concentration index, creatinine concentration index and renal index of lesion. Material and methods. The study included 85 patients with obstructive icterus (50 patients before surgical intervention and 35 after surgical intervention) and 30 patients without icterus as a control group. The patients with normal renal function before the development of the disease were included. Results. Malignant etiology was present in 39 patients and benign in 46 patients of the examined group. The evaluation parameters of renal function were examined in all of the patients. Creatinine concentration index led to the greatest change in the coefficient value of an internal consistency, showing that it was the best renal function marker in the examined group of patients with icterus. The next one was the urinary osmolality, since its exclusion would lead to a decrease in the value of Cronbach ? coefficient to 0.06. Icterus and surgical intervention show statistically significant effects to change in the value of the markers of laboratory differentiation of renal function, observed as an entire set. Discussion and conclusion. The examination showed that the concentration clearances of creatinine and urine osmolality are the parameters which point to the probability of renal dysfunction occurrence in obstructive icterus.

scholarly journals PHYTOCHEMICAL ANALYSIS AND COMPARATIVE ANTIPARKINSON ACTIVITY OF FOUR SPECIES OF MUCUNA

2018 ◽  
Vol 11 (7) ◽  
pp. 125
Author(s):  
Karunanithi M ◽  
David Raj C ◽  
Brindha P ◽  
Jegadeesan M ◽  
Kavimani S
Keyword(s):  
Mucuna Pruriens ◽  
Control Group ◽  
Phytochemical Analysis ◽  
Tongue Protrusion ◽  
Phytochemical Study ◽  
P Values ◽  
Dose Levels ◽  
Chewing Movement ◽  
Vacuous Chewing ◽  
Seed Extracts

Objective: The aim was to study the antiparkinson activity in the seed extracts of four species of Mucuna.Methods: The hydroalcoholic extracts of seeds of four species of Mucuna were evaluated for antiparkinson activity of after a preliminary phytochemical study. The activity was measured in rats by indirectly measuring the decrease in malondialdehyde level, decrease in tongue protrusion frequency, and reduction in vacuous chewing movement after administering reserpine at the dose of 1 mg/kg. The dose levels of four species of Mucuna seed extract were kept at 100, 200, and 300 mg/Kg.Results: Extracts exhibited potent antiparkinson activity and achieved statistically significant p values compared with control group. The study corroborates and compares all four species of Mucuna. Conclusion: Among the extracts, the highest percentage of antiparkinson activity was recorded for Mucuna pruriens.

scholarly journals Population Pharmacokinetic Analysis of Vancomycin Using Serum Cystatin C as a Marker of Renal Function

2009 ◽  
Vol 54 (2) ◽  
pp. 778-782 ◽  
Author(s):  
Akihiro Tanaka ◽  
Tetsuya Aiba ◽  
Takashi Otsuka ◽  
Katsuya Suemaru ◽  
Tatsuya Nishimiya ◽  
...  
Keyword(s):  
Renal Function ◽  
Cystatin C ◽  
Predictive Performance ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
New Model ◽  
The Mean

ABSTRACT We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min] = 0.825 × GFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (−3.45 to −1.38) of the difference in each value of the mean absolute error (−2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.

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